I looked at them and passed. I typically do not get into biotech firms in that early a stage of Trials and when I was looking at them I saw some red flags. Good luck with it but it's just not my thing.
I don't post on a board if I don't hold the stock and I haven't taken a position (yet) in HZNP.
As to there being a "delay" regarding NVIV, actually just the opposite is true. The CEO estimates an approval date of 2017 on the Acute SCI treatment when the prior "consensus" (as much as you ever see such a thing) was 2018 and there's now a clear path to approval for the Chronic SCI treatment that they have developed (pre-IND meeting with the FDA in 2016.
They are being completely consistent with their stated policy. As to "hiding something" I think that the actions of the FDA are a pretty fair indication that nothing is being hidden that should be disclosed. Even in an Open Study, patient confidentiality is pretty much the FDA's watchword here.
The Primary Endpoint is the ASIA Score Conversion with a Secondary Endpoint which includes a broad and flexible range of improvements. In order to understand how that works you need to understand the relationship between "Primary" and "Secondary" endpoints. It's not a situation where one Endpoint is more important than the other so much as it is a situation where the Secondary Endpoint provides criteria that may provide a basis for approval where the Primary Endpoint is not met.
In any event in INSPIRE the FDA is not technically limited to consideration of either the Primary or Secondary Endpoint because of the general prohibition against using Clinical Data in HDE Approvals. First, last and always the thing that the FDA will key to most is the continued absence of medically significant Adverse Events. As long as we continue to have no AE's reported virtually any progress noted with either the Primary or Secondary Endpoints will be adequate to gain approval.
Forest. Trees. NO single patient's progress (or lack thereof) is crucial to the success here. Yes, the data accumulates "bottom up". However there should be no expectation that every patient should experience improvements. Which is why I have contended from the get-go that anticipating individual progress updates is rather a fool's errand.
First of all we have no basis to expect that the majority of patient progress will EVER be communicated (other than the very narrow guidance given by the company). Second, the FDA doesn't give a hoot about the success of any single patient; with the HDE their main focus (until the entire population has been treated) will be the absence of adverse events attributable to the therapy. Finally, even those patients who do not respond may shed important information as to why other patients did respond, so even a so-called therapeutic "failure" can still be a success in HDE-Land.
You are correct - and insurance reimbursement is a whole other topic, but certainly an important one. HUD-approved devices generally don't have difficulty in gaining coverage from Private Insurers or Medicare principally because they specifically address unmet therapeutic or diagnostic needs. Insurance coverage really should not be an issue if the NSS gains marketing authorization under the HUD.
Read THIS thread and you will see that my point is that a focus on the ASIA Score, even though it is the Primary Endpoint for INSPIRE, is somewhat misleading in the context of the HDE. In the broadest sense of course every improvement is another "notch in the gun". In fact the broader range of response that can be in any way attributed to the NSS the better. But that isn't really the point here and again as a practical matter the only crucial events that can originate with any specific patient update is not therapeutic improvement but a show-stopping catastrophic adverse event.
There is (and has been) because of the nature of this Study a misleading emphasis on individual patient updates. It's understandable, but misleading. It is the cumulative effects across the scope of the entire Study that is important. A patient who does not respond can yield as important a data point as any who do.
As a practical matter, no, it doesn't; not with 15 more patients in the "pool", at least not progress specific to AISA conversion. You have both Primary and Secondary endpoints to consider in INSPIRE as well as the mandate to CDRH not to be constrained to Clinically-derived data.
No question that the FDA has been pretty accommodating here, just as they should be. I would say that we are most assuredly "on track" for approval.
And that's kind of the point. The HUD/HDE is designed to do just that. Unlike a PMA it is designed to allow for access to therapies that essentially "do more good than harm". They're still considered "experimental" and the bar for their approval is set purposefully low.
Kind of my point: the "approval net" for therapies like this is purposefully cast quite wide. A Discrete Primary Endpoint can make the approval administratively more simple (and the FDA loves administrative simplicity) but the whole HDE process is designed to permit for the use of much more qualitative factors which may actually be more important than the Primary Endpoint.
In another post I said that the FDA (absent any other factors) might want to see, say, 33%. In reality it's probably not really going to be that arbitrary in the least. It's possible that you could hit a response lower than the 16% (tough as a practical matter in a Study this small but bear with me) and still get approved or a response of 70% and not get approved (again, incredibly unlikely but possible on a really weird "fringe" basis) simply because the numbers are not the driving factor in any of this.
My point was that really we could see a raging debate on the numbers here that isn't actually germane to the issue at hand because in a very real sense "the numbers" don't actually drive the approval determination.
You all might as well stop crunching those numbers right now because there are many other much more important factors that will apply in making a determination of Probable Benefit other than how many out of twenty patients convert from AISA-A. Yes, it's the Primary Endpoint, no doubt one that was selected because it presents a very simple basis for approval if more than 3.2 patients meet that goal. (2 down and 1.2 to go, I guess). But it's not the only item in the Probable Benefit Box.
Patient 2 is still ASIA-A, but has demonstrated a list of benefits as long as your arm. The FDA won't ignore that. We don't know diddly about Patients 4 or 5 yet other than the fact that they have not yet converted. We don't know if they had related trauma that might have effected that, what the time to treat was or what their general physical condition was. And we do not know what other improvements, significant as relevant to their original condition but not individually "dramatic" may have been realized.
No two patients are identical, even in terms of their recuperative ability. All we know is that nothing "dramatic" (I will not use the word "material" because NOTHING that happens to a single patient other than an adverse event directly attributable to the NSS that might be adequate for the FDA to pull the plug here is "material") has happened either way.
The determination of Probable Benefit is not a "numbers game". We should stop treating it as if it is.
If I had a nickel for every time I was told that patients would "be lining up" for a new therapy I'd have lots and lots of nickels. That's even more the case where an unmet medical need is concerned.
Uptake for a new therapy is almost always a bit of a challenge. The primary tool in meeting that challenge, particularly with an HUD which can advertised as being neither Safe nor Effective is the existing case history data from treated patients. The more of those you have in hand the better off you are. The bottom line is that even with HUD approval you are still, technically, dealing with an "experimental therapy" and one which will not have the liability protections that it enjoys during the Pilot and Pivotal Studies. So, yeah, we're going to have some convincing to do and the more bullets in the gun, the better.
I think that 33% isn't an unreasonable bar, but that's just me. We don't need to meet 16%, but beat it, and rather soundly. Because if we don't it will be tough to get our full allocation of sites and even tougher for those sites to get outside referrals.
No, because exceeding the historical registry for improvement is not the only reason to conduct a Pivotal Study under the HDE.
Yes, of course the Probable Benefit and Safety profiles have to be attained, but additionally the case histories for the Study patients comprise the single most important information which can be used by the company in "selling" the NSS to physicians (actually to convince those physicians to refer patients to one of the approved Sites for treatment). Additionally the Study should disclose something of a patient profile for those most likely to benefit from the surgery.
The historical bar is 16% and the bar for approval won't probably be a lot higher than that - perhaps 33%. But a one in three shot at improvement may not be adequate to convince patients and their physicians to give the therapy a shot unless there is adequate supporting information to assist in that decision process.
An early halt to the Pivotal is a two-edged sword. Yes, it would permit earlier commercialization but on the other hand it could severely limit the rate of adoption for this therapy following approval.
If that should happen they still are looking at an IND application for Chronic SCI treatment that has nothing to do with the Scaffold in 2017 which represents a much larger patient population. Frankly if that approach is successful it would probably replace the Scaffold as a treatment alternative in any case.
About as drastic as you can imagine.
I expect that eventually the "Trails" approach (or some derivative of it) will be the standard of care for both Acute and Chronic SCI. The NSS itself seems to impart some degree of benefit but (assuming that the information that we have is accurate) it will eventually be supplanted by a Stem Cell based therapy.
As to the level of injury as a factor in recovery it actually appears that the most improvement is seen with patients who are treated as closely as possible to the time of injury. But, again, I'm drawing that conclusion from a very small data set.
Not really. Until we know what the pricing here is going to look like on the NSS all you can really say with any certainty is that the Market Cap in 2016 really should be much higher than it is today, and for now that's good enough.
If the FDA actually "closes out" the Pilot (as I think they will) after the Six Month Assessments for Patients 1-5 then recruiters will be able to say "We successfully completed the Pilot Study" which should be a "plus". In general though it just becomes easier to recruit new patients into a Study as more patients have been treated successfully (without adverse events).
The protocol will stay risk-weighted. That never changes. But the answer to the underlying question "Will this kill me? Will this make me worse?" can be honestly answered upon completion of the Pilot by saying that the (Safety) Study has been completed with no adverse events reported. That changes the dynamic considerably.